WNT-1 expression in basal cell carcinoma of head and neck. An immunohistochemical and confocal study with regard to the intracellular distribution of beta-catenin

Background: The WNT gene family is a group of developmental genes involved in cell growth regulation, differentiation and organogenesis in both vertebrates and invertebrates. These genes are also involved in oncogenesis: beta-catenin, a component of the WNT pathway, has been reported to be involved in the genesis of numerous human cancers. WNT-1 pathway signaling is mediated via interactions between beta-catenin, a multifunctional protein playing an important role in cell-to-cell adhesion and gene expression, and members of the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta-catenin protein and determines its accumulation in the cytoplasm and nucleus. Materials and Methods: In order to evaluate the role of WNT-1 in the neoplastic progression of basal cell carcinoma (BCC), an immunohistochemical and confocal study of its expression and its correlation with beta-catenin distribution was performed in 46 selected cases of BCCs of the head and neck region. Results: While normal skin showed a WNT-1-positive staining only of the cutaneous annexa and a few cells in the basal/parabasal layers, the areas of de-differentiated BCCs showed a high granular positive staining (50-80% of cells). On the other hand, normal skin was characterized by an intense membranous staining for beta-catenin, with a progressive displacement of the signal toward the periphery of the cells. In BCC the absence of membrane localization and cytosolic staining for beta-catenin were detected in de-differentiated cases. A significant correlation (by Pearson's analysis) between overexpression of WNT-1 and free pools of beta-catenins was observed in these tumors. Conclusion: According to these data, the potential role of the WNT-1 gene in BCC seems to correlate with its ability to induce elevated cytoplasmic beta-catenin levels, suggesting that the WNT-1 gene can activate an intracellular signaling pathway involved in the process of cell transformation